To demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized MG. [ Time Frame: 1 day ] [ Designated as safety issue: No ]

In this hypothesis-generating Phase II study, multiple assessments of skeletal muscle function and fatigability will be made without specifying a single primary endpoint, including:

To evaluate and characterize the relationship, if any, between the doses and plasma concentrations of CK-2017357 and its pharmacodynamic effects (PK/PD relationship) [ Time Frame: 2 days ] [ Designated as safety issue: No ]

To evaluate the safety and tolerability of CK-2017357 administered as single oral doses to patients with MG [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

To evaluate the effect of CK-2017357 on investigator and patient determined global functional assessment and the Modified MG Symptom Score [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Original Secondary Outcome Measures ICMJE

Same as current

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).

Detailed Description

This study is a Phase II, double-blind, randomized, three-way crossover, placebo-controlled, PD study of CK-2017357 in patients with generalized MG on standard therapy. 36 to 78 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 250 mg, and 500 mg of CK-2017357. All six treatment sequences will enroll 6 patients. A wash out period of at least 7 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on measures of muscle strength, muscle fatigue and pulmonary function utilizing the standardized Quantitative MG (QMG) score and Manual Muscle Test (MMT). The pharmacokinetic (PK) and pharmacodynamic (PD) relationship of CK-2017357 after two single doses will be assessed versus placebo, and the CK-2017357 concentration versus time data obtained in this study may be used to develop a population PK model to estimate intra- and inter-patient variability of PK parameters in patients with MG.

Ability to refrain from IVIg treatments during the course of the study

Ability to refrain from cholinesterase-inhibitors (e.g. pyridostigmine) for 12 hours before each dose

Ability to perform all elements of the QMG

Grade of 2 or 3 in two or more of the following muscle groups as measured by QMG: right or left arm flexion, head lift, and right or left leg raise at 45° Note: Patients may re-screen if they fail due to inadequate weakness from taking pyridostigmine within 12 hours of screening

Body mass index (BMI) of 18.0 to 36.0 kg/m2, inclusive

Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within the normal range, or if outside of the normal range, deemed not clinically significant by the Investigator

to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) for the duration of the study and 10 weeks after the end of the study or b. to abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

The following criteria exclude potential patients from the study:

History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue

Other major chronic or debilitating illnesses within six months prior to study entry

Receipt of IVIg or plasmapheresis treatment within 6 weeks prior to the first dose of study drug

Changes to immunosuppressive treatments (i.e., prednisone) within 6 weeks prior to the first dose of study drug

Rituxan treatment within 3 months prior to study entry

Participation in any other investigational study drug or device trial in which receipt of an investigational study drug or device occurred within 30 days prior to dosing

Any prior treatment with CK-2017357

Recent history of alcoholism or drug abuse, or significant behavioral or psychiatric problems, or other conditions which in the Investigator's opinion may impair ability to adequately comply with the requirements of the study

Gender

Both

Ages

18 Years to 80 Years (Adult, Senior)

Accepts Healthy Volunteers

No

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects